tbuckley/cabot-search huggingface dataset:
Comparison of Semen Quality Before and After Inactivated SARS-CoV-2 Vaccination Among Men in China
Authors: Jialyu Huang, Leizhen Xia, Lifeng Tian, Dingfei Xu, Zheng Fang, Jiaying Lin, Qiongfang Wu
Journal: JAMA Network Open (2022)

This cohort study examines changes in semen quality—including semen volume, sperm concentration, total sperm count, and total and progressive sperm motility—before and after inactivated SARS-CoV-2 vaccination among men in China.
Sociodemographic Characteristics and Comorbidities of Patients With Long COVID and Persistent Olfactory Dysfunction
Authors: Alna Carolina Mendes Paranhos, Ápio Ricardo Nazareth Dias, Livia Caroline Machado da Silva, Gisele Vieira Hennemann Koury, Emanuel de Jesus Sousa, Antônio José Cerasi, Givago Silva Souza, Juarez Antônio Simões Quaresma, Luiz Fábio Magno Falcão
Journal: JAMA Network Open (2022)

Determining the characteristics, type, and severity of olfactory dysfunction in patients with long COVID is important for the prognosis and potential treatment of the affected population.To describe the sociodemographic and clinical features of patients with long COVID who develop persistent olfactory dysfunction.This cross-sectional study, conducted at a rehabilitation center at a public university in the Amazon region of Brazil between September 9, 2020, and October 20, 2021, comprised 219 patients with long COVID and self-reported neurologic symptoms. Of these 219 patients, 139 received a diagnosis of chronic olfactory dysfunction, as confirmed by the Connecticut Chemosensory Clinical Research Center (CCCRC) test.Clinical diagnosis of long COVID.Electronic case report forms were prepared for the collection of sociodemographic and clinical data. Patients' sense of smell was evaluated via a CCCRC test, and the association of olfactory dysfunction with aspects of daily life was recorded using a questionnaire.Of the 219 patients included in the study, 164 (74.9%) were women, 194 (88.6%) were between 18 and 59 years of age (mean [SD] age, 43.2 [12.9] years), 206 (94.1%) had more than 9 years of education, and 115 (52.5%) had a monthly income of up to US $192.00. In the study group, 139 patients (63.5%) had some degree of olfactory dysfunction, whereas 80 patients (36.5%) had normosmia. Patients with olfactory dysfunction had a significantly longer duration of long COVID symptoms than those in the normosmia group (mean [SD], 242.7 [101.9] vs 221.0 [97.5] days; P = .01). Among patients with anosmia, there was a significant association between olfactory dysfunction and daily activities, especially in terms of impairment in hazard detection (21 of 31 patients [67.7%]), personal hygiene (21 of 31 patients [67.7%]), and food intake (21 of 31 patients [67.7%]). Univariable logistic regression analyses found that ageusia symptoms were associated with the occurrence of olfactory dysfunction (odds ratio [OR], 11.14 [95% CI, 4.76-26.07]; P < .001), whereas headache (OR, 0.41 [95% CI, 0.22-0.76]; P < .001) and sleep disorders (OR, 0.48 [95% CI, 0.26-0.92]; P = .02) showed an inverse association with the occurrence of olfactory dysfunction.Olfactory dysfunction is one of the most important long-term neurologic symptoms of COVID-19, with the highest prevalence seen among women, adults, and outpatients. Patients with olfactory dysfunction may experience persistent severe hyposmia or anosmia more than 1 year from the onset of symptoms, suggesting the possibility of the condition becoming a permanent sequela.
Analysis of Vaccine Reactions After COVID-19 Vaccine Booster Doses Among Pregnant and Lactating Individuals
Authors: Alisa Kachikis, Janet A. Englund, Isabela Covelli, Yael Frank, Candace Haghighi, Michael Singleton, Alison L. Drake, Linda O. Eckert
Journal: JAMA Network Open (2022)

<h3>Importance</h3> COVID-19 vaccine boosters or third doses are recommended for adolescents and adults who completed their initial COVID-19 vaccine course more than 5 months prior. Minimal data are available on COVID-19 vaccine booster or third dose reactogenicity among pregnant and lactating individuals. <h3>Objective</h3> To describe the reactions to the booster or third dose of the COVID-19 vaccine and vaccine experiences among pregnant and lactating individuals. <h3>Design, Setting, and Participants</h3> Beginning in October 2021, a follow-up Research Electronic Data Capture (REDCap) survey regarding a COVID-19 vaccine booster or third dose was sent to 17 504 participants in an ongoing online prospective cohort study on COVID-19 vaccines among pregnant and lactating individuals. A convenience sample of adults enrolled in the online prospective study who were pregnant, lactating, or neither pregnant nor lactating at the time of their booster or third dose was eligible for this follow-up survey; 17 014 (97.2%) completed the follow-up survey. <h3>Exposure</h3> Receipt of a booster or third dose of the COVID-19 vaccine. <h3>Main Outcomes and Measures</h3> Self-reported vaccine reactions less than 24 hours after the dose. <h3>Results</h3> As of April 4, 2022, 17 014 eligible participants (mean [SD] age, 33.3 [3.5] years) responded to the booster or third dose survey; of these, 2009 (11.8%) were pregnant at the time of their booster or third dose, 10 279 (60.4%) were lactating, and 4726 (27.8%) were neither pregnant nor lactating. After a COVID-19 booster or third dose, most individuals (14 074 of 17 005 [82.8%]) reported a local reaction, and 11 542 of 17 005 (67.9%) reported at least 1 systemic symptom. Compared with individuals who were neither pregnant nor lactating, pregnant participants were more likely to report any local reaction to a COVID-19 booster or third dose (adjusted odds ratio [aOR], 1.2; 95% CI, 1.0-1.4;<i>P</i> = .01) but less likely to report any systemic reaction (aOR, 0.7; 95% CI, 0.6-0.8;<i>P</i> &lt; .001). Most pregnant (1961 of 2009 [97.6%]) and lactating (9866 of 10 277 [96.0%]) individuals reported no obstetric or lactation concerns after vaccination. <h3>Conclusions and Relevance</h3> This study suggests that COVID-19 vaccine boosters or third doses were well tolerated among pregnant and lactating individuals. Data to evaluate tolerability of boosters or additional doses among pregnant and lactating individuals will be important as they are considered for these populations.
Table of Contents
Authors: P Beer, A Biankin, A Oaknin, T Bosse, C Creutzberg, G Giornelli, P Harter, F Joly, D Lorusso, C Marth, V Makker, M Mirza, J Ledermann, N Colombo, M Maio, E Basch, F Denis, L Fallowfield, P Ganz, D Howell, C Kowalski, F Perrone, A Stover, P Sundaresan, L Warrington, L Zhang, K Apostolidis, J Freeman-Daily, C Ripamonti, D Santini, F Cortiula, B Reymen, S Peters, P Van Mol, E Wauters, J Vansteenkiste, D De Ruysscher, L Hendriks, A Bessede, A Marabelle, J Guégan, F Danlos, S Cousin, F Peyraud, N Chaput, M Spalato, G Roubaud, M Cabart, M Khettab, A Chaibi, C Rey, I Nafia, F Mahon, J Soria, A Italiano, G Ghilardi, E Chong, J Svoboda, P Wohlfarth, S Nasta, S Williamson, J Landsburg, J Gerson, S Barta, R Pajarillo, J Myers, A Chen, L Schachter, R Yelton, H Ballard, A Dwinal, S Gier, D Victoriano, E Weber, E Napier, A Garfall, D Porter, U Jäger, R Maziarz, M Ruella, S Schuster, P Ascierto, L Manzyuk, D Motola-Kuba, N Penel, P Cassier, G Bariani, A De, Jesus Acosta, T Doi, F Longo, W Miller, D.-Y Oh, M Gottfried, L Xu, F Jin, K Norwood, E Pleasance, A Bohm, L Williamson, J Nelson, Y Shen, M Bonakdar, E Titmuss, V Csizmok, K Wee, S Hosseinzadeh, C Grisdale, C Reisle, G Taylor, E Lewis, M Jones, D Bleile, S Sadeghi, W Zhang, A Davies, B Pellegrini, T Wong, R Bowlby, S Chan, K Mungall, E Chuah, A Mungall, R Moore, Y Zhao, B Deol, A Fisic, A Fok, D Regier, D Weymann, D Schaeffer, S Young, S Yip, K Schrader, N Levasseur, S Taylor, X Feng, A Tinker, K Savage, S Chia, K Gelmon, S Sun, H Lim, D Renouf, S Jones, M Marra, J Laskin, A Pra, P Ghadjar, S Hayoz, V Liu, D Spratt, D Thompson, E Davicioni, H.-C Huang, X Zhao, Y Liu, C Schär, P Gut, L Plasswilm, T Hölscher, B Polat, G Hildebrandt, A.-C Müller, A Pollack, G Thalmann, D Zwahlen, D Aebersold
Journal: Annals of Oncology (2022)
HIV incidence estimation among female sex workers in South Africa: a multiple methods analysis of cross-sectional survey data
Authors: Reshma Kassanjee, Alex Welte, Kennedy Otwombe, Maya Jaffer, Minja Milovanovic, Khuthadzo Hlongwane, Adrian J Puren, Naomi Hill, Venice Mbowane, Kristin Dunkle, Glenda Gray, Fareed Abdullah, Rachel Jewkes, Jenny Coetzee
Journal: The Lancet HIV (2022)
Rezvilutamide versus bicalutamide in combination with androgen-deprivation therapy in patients with high-volume, metastatic, hormone-sensitive prostate cancer (CHART): a randomised, open-label, phase 3 trial
Authors: Weijie Gu, Weiqing Han, Hong Luo, Fangjian Zhou, Dalin He, Lulin Ma, Hongqian Guo, Chaozhao Liang, Tie Chong, Jun Jiang, Zhiwen Chen, Yong Wang, Qing Zou, Ye Tian, Jun Xiao, Jian Huang, Shaoxing Zhu, Qiang Dong, Xiaoping Zhang, Hanzhong Li, Xinfeng Yang, Chunxia Chen, Junliang Li, Chunlei Jin, Xiaojing Zhang, Dingwei Ye
Journal: The Lancet Oncology (2022)
Paediatric patients with heterozygous familial hypercholesterolaemia treated with evolocumab for 80 weeks (HAUSER-OLE): a single-arm, multicentre, open-label extension of HAUSER-RCT
Authors: Raul D Santos, Andrea Ruzza, G Kees Hovingh, Claudia Stefanutti, François Mach, Olivier S Descamps, Jean Bergeron, Bei Wang, Andrea Bartuli, Paola Sabrina Buonuomo, Susanne Greber-Platzer, Ilse Luirink, Ajay K Bhatia, Frederick J Raal, John J P Kastelein, Albert Wiegman, Daniel Gaudet
Journal: The Lancet Diabetes & Endocrinology (2022)
Towards the elimination of chronic obstructive pulmonary disease: a Lancet Commission
Authors: Daiana Stolz, Takudzwa Mkorombindo, Desiree M Schumann, Alvar Agusti, Samuel Y Ash, Mona Bafadhel, Chunxue Bai, James D Chalmers, Gerard J Criner, Shyamali C Dharmage, Frits M E Franssen, Urs Frey, MeiLan Han, Nadia N Hansel, Nathaniel M Hawkins, Ravi Kalhan, Melanie Konigshoff, Fanny W Ko, Trisha M Parekh, Pippa Powell, Maureen Rutten-van Mölken, Jodie Simpson, Don D Sin, Yuanlin Song, Bela Suki, Thierry Troosters, George R Washko, Tobias Welte, Mark T Dransfield
Journal: The Lancet (2022)
Surface Bandgap Engineering of Nanostructured Implants for Rapid Photothermal Ion Therapy of Bone Defects
Authors: Yang Xue, Lan Zhang, Fuwei Liu, Yiwei Zhao, Jianhong Zhou, Yan Hou, Han Bao, Liang Kong, Fei Ma, Yong Han
Journal: Advanced Healthcare Materials (2022)

Abstract Bone defects are seriously threatening the health of orthopedics patients and it is difficult for implants to accelerate bone regeneration without using bone growth factors. Herein, a fast photothermal ion therapeutic strategy is developed based on the bandgap engineering of nanostructured TiO 2 through (Si/P)‐dual elemental doping by micro‐arc oxidation treatment of titanium implants. The (Si/P)‐dual doping can tune the surface bandgap structure of TiO 2 by decreasing bandgap and broadening valence band simultaneously, which is confirmed by density functional theory calculations. It not only endows the implants with a mildly photothermal effect under near‐infrared (NIR) light irradiation, but also creates an (Si/P) ion‐rich microenvironment around the implants. This photothermal ion microenvironment can tune the behaviors of osteoblasts by promoting p38/Smad and ERK signaling pathways of osteoblasts, thus significantly upregulating the expression of osteogenesis genes by the synergistic action of mild photothermal stimulation and increased release of Si/P ions. The in vivo results are also in good agreement with in vitro tests, i.e., under NIR light irradiation, the photothermally responsive TiO 2 enhances the bone formation and osteointegration with implants. Therefore, this kind of photothermal ion strategy is a promising remote and noninvasive therapeutic mode for promoting bone regeneration of Ti implants.
The bacterial effector GarD shields Chlamydia trachomatis inclusions from RNF213-mediated ubiquitylation and destruction
Authors: Stephen C. Walsh, Jeffrey R. Reitano, Mary S. Dickinson, Miriam Kutsch, Dulcemaria Hernandez, Alyson B. Barnes, Benjamin H. Schott, Liuyang Wang, Dennis C. Ko, So Young Kim, Raphael H. Valdivia, Robert J. Bastidas, Jörn Coers
Journal: Cell Host & Microbe (2022)
Digital spatial profiling to uncover biomarkers of immunotherapy outcomes in head and neck squamous cell carcinoma.
Authors: Niki Gavrielatou, Ioannis Vathiotis, Thazin Nwe Aung, Saba Shafi, Sneha Burela, Aileen Fernandez, Amanda Psyrri, David L. Rimm
Journal: Journal of Clinical Oncology (2022)

6050 Background: Immunotherapy (ITx) has become the standard of care in the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, response rate is limited to 13-18% of patients, underlining the need to identify mechanisms implicated in response or resistance. This study aims to uncover novel biomarkers of ITx outcomes in R/M HNSCC using digital spatial profiling (DSP) technology. Methods: Pre-treatment biopsy samples of 50 ITx-treated R/M HNSCC patients, constructed in the form of tissue microarray (YTMA496), were included in our discovery cohort. Cases underwent DSP with the Human Immuno-Oncology protein panel (NanoString Technologies), comprising 71 photocleavable oligonucleotide-labeled primary antibodies, used for target-protein quantification in 4 distinct molecularly defined compartments: tumor (CK+), leukocyte (CD45+), macrophage (CD68+) and immune stroma (CD45+/CD68+). All markers were explored for associations with progression-free (PFS) and overall survival (OS) using a univariate Cox regression model. Significant markers were validated using an alternative quantitative immunofluorescence method as well as in an independent validation cohort of 29 ITx-treated R/M HNSCC cases (YTMA523). Results: Univariate DSP data analysis revealed high beta2-microglobulin (B2M), LAG-3, CD25 and 4-1BB in tumor, high B2M, CD45 and CD4 in stroma, and low fibronectin in the macrophage compartment, as markers associated with improved PFS. Increased levels of B2M and CD25 in tumor and CD11c in stroma were also correlated with prolonged OS. Focusing on B2M, cases at the top tertile of tumor B2M expression were associated with improved PFS and OS [HR, 0.43; 95% confidence interval (CI), 0.21-0.9; p = 0.034 and HR, 0.41; 95% CI, 0.18-0.90; p = 0.047, respectively], by an orthogonal QIF method. Findings were replicated in our validation cohort for PFS [HR, 0.41; 95% CI, 0.19-0.93; p = 0.034] and showed a similar trend for OS [HR, 0.44; 95% CI, 0.19-1.0; p = 0.074]. B2M-high tumors also had significant enrichment with immune-cell markers (CD3, CD4, CD8, CD11c, CD68 and CD163) and increased immune checkpoint expression (PD-L1, ICOS, TIM-3, LAG-3, IDO1, B7-H3), predominantly in the tumor compartment. Conclusions: Our study indicates that intact, highly functional antigen presentation, sustained by high B2M expression in tumor, confers survival benefit in ITx treated R/M HNSCC patients, an effect driven by increased intra-tumoral immunogenicity.
Blood Pressure Classification Using the 2017 ACC/AHA Guideline and Heart Failure in Patients With Cancer
Authors: Hidehiro Kaneko, Yuichiro Yano, Hokyou Lee, Hyeok-Hee Lee, Akira Okada, Yuta Suzuki, Hidetaka Itoh, Satoshi Matsuoka, Katsuhito Fujiu, Nobuaki Michihata, Taisuke Jo, Norifumi Takeda, Hiroyuki Morita, Akira Nishiyama, Koichi Node, Hyeon Chang Kim, Hideo Yasunaga, Issei Komuro
Journal: Journal of Clinical Oncology (2022)

Despite the growing recognition of the importance of hypertension in patients with cancer, little is known about whether high blood pressure (BP) among patients with cancer is associated with incident heart failure (HF) and other cardiovascular disease (CVD) events and what BP levels are linked to these events. We examined the association of BP classification on the basis of the 2017 American College of Cardiology/American Heart Association BP guideline with the risk of HF and CVD events in patients with cancer.We studied 33,991 patients with a history of breast, colorectal, or stomach cancer (median age, 53 years; 34.1% men). Patients receiving treatment with BP-lowering medications or having a history of CVD including HF were excluded. Using BP measurements at baseline, 33,991 participants were categorized as having normal BP (n = 17,444), elevated BP (n = 4,733), stage 1 hypertension (n = 7,502), or stage 2 hypertension (n = 4,312). The primary outcome was HF.Over a mean follow-up of 2.6 ± 2.2 years, 779 HF events were recorded. After multivariable adjustment, the hazard ratios (HRs) for HF were 1.15 (95% CI, 0.93 to 1.44) for elevated BP, 1.24 (95% CI, 1.03 to 1.49) for stage 1 hypertension, and 1.99 (95% CI, 1.63 to 2.43) for stage 2 hypertension. A stepwise increase in risk with BP categories was also observed in other CVD events. This association was observed even in patients undergoing active cancer treatment. The relationship between hypertension and the risk of developing HF in patients with cancer was confirmed in the Korean National Health Insurance Service database.Medication-naïve stage 1 and 2 hypertension was associated with a greater risk of HF and other CVD events in patients with cancer. Our results suggest the importance of multidisciplinary collaboration (eg, oncologists and cardiologists) to establish the optimal management strategy for hypertension in patients with cancer.
Risk Factors for Heart Failure Among Pan-European Childhood Cancer Survivors: A PanCareSurFup and ProCardio Cohort and Nested Case-Control Study
Authors: Esmée C. de Baat, Elizabeth A.M. Feijen, Raoul C. Reulen, Rodrigue S. Allodji, Francesca Bagnasco, Edit Bardi, Fabiën N. Belle, Julianne Byrne, Elvira C. van Dalen, Ghazi Debiche, Ibrahima Diallo, Desiree Grabow, Lars Hjorth, Momcilo Jankovic, Claudia E. Kuehni, Gill Levitt, Damien Llanas, Jacqueline Loonen, Lorna Z. Zaletel, Milena M. Maule, Lucia Miligi, Helena J.H. van der Pal, Cécile M. Ronckers, Carlotta Sacerdote, Roderick Skinner, Zsuzsanna Jakab, Cristina Veres, Nadia Haddy, David L. Winter, Florent de Vathaire, Michael M. Hawkins, Leontien C.M. Kremer
Journal: Journal of Clinical Oncology (2022)

Heart failure (HF) is a potentially life-threatening complication of treatment for childhood cancer. We evaluated the risk and risk factors for HF in a large European study of long-term survivors. Little is known of the effects of low doses of treatment, which is needed to improve current treatment protocols and surveillance guidelines.This study includes the PanCareSurFup and ProCardio cohort of ≥ 5-year childhood cancer survivors diagnosed between 1940 and 2009 in seven European countries (N = 42,361). We calculated the cumulative incidence of HF and conducted a nested case-control study to evaluate detailed treatment-related risk factors.The cumulative incidence of HF was 2% (95% CI, 1.7 to 2.2) by age 50 years. The case-control study (n = 1,000) showed that survivors who received a mean heart radiation therapy (RT) dose of 5 to < 15 Gy have an increased risk of HF (odds ratio, 5.5; 95% CI, 2.5 to 12.3), when compared with no heart RT. The risk associated with doses 5 to < 15 Gy increased with exposure of a larger heart volume. In addition, the HF risk increased in a linear fashion with higher mean heart RT doses. Regarding total cumulative anthracycline dose, survivors who received ≥ 100 mg/m2 had a substantially increased risk of HF and survivors treated with a lower dose showed no significantly increased risk of HF. The dose-response relationship appeared quadratic with higher anthracycline doses.Survivors who received a mean heart RT dose of ≥ 5 Gy have an increased risk of HF. The risk associated with RT increases with larger volumes exposed. Survivors treated with < 100 mg/m2 total cumulative anthracycline dose have no significantly increased risk of HF. These new findings might have consequences for new treatment protocols for children with cancer and for cardiomyopathy surveillance guidelines.
NCCN Guidelines® Insights: Ovarian Cancer, Version 3.2022
Authors: Deborah K. Armstrong, Ronald D. Alvarez, Floor J. Backes, Jamie N. Bakkum-Gamez, Lisa Barroilhet, Kian Behbakht, Andrew Berchuck, Lee-may Chen, Viola C. Chitiyo, Mihaela Cristea, Maria DeRosa, Eric L. Eisenhauer, David M. Gershenson, Heidi J. Gray, Rachel Grisham, Ardeshir Hakam, Angela Jain, Amer Karam, Gottfried E. Konecny, Charles A. Leath III, Gary Leiserowitz, Joyce Liu, Lainie Martin, Daniela Matei, Michael McHale, Karen McLean, David S. Miller, Sanja Percac-Lima, Steven W. Remmenga, John Schorge, Daphne Stewart, Premal H. Thaker, Roberto Vargas, Andrea Wahner Hendrickson, Theresa L. Werner, Emese Zsiros, Mary A. Dwyer, Lisa Hang
Journal: Journal of the National Comprehensive Cancer Network (2022)

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years following diagnosis. The NCCN Guidelines for Ovarian Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with ovarian, fallopian tube, and primary peritoneal cancers. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised guidance on alternative chemotherapy regimens for patients with advanced age and/or comorbidities, a new algorithm for recurrent low-grade serous carcinoma based on developing research and novel therapeutic agents, and updated language regarding tumor molecular analysis applications in ovarian cancer.
Prevalence of Breast Cancer Survivors Among Canadian Women
Authors: Amy A. Kirkham, Katarzyna J. Jerzak
Journal: Journal of the National Comprehensive Cancer Network (2022)

The 49% decrease in breast cancer mortality since 1986 has increased the number of breast cancer survivors requiring survivorship care. The purpose of this analysis was to estimate the 2022 prevalence of breast cancer survivors diagnosed within the past 15 years among Canadian women.We extracted the projected female breast cancer cases from 2007 to 2021 and rates of net survival (competing noncancer causes of death removed) from the Canadian Cancer Society's statistical reports. Overall survival was extracted from published Ontario data. Using known survival rates for 1, 5, 10, and 15 years, we interpolated remaining years and applied the corresponding net and overall survival rates to the projected cases for each year from 2007 to 2021 to determine survivors in 2022. Prevalence for predefined age groups was also calculated. As an example of excess healthcare costs attributable to breast cancer, we calculated the excess costs of heart failure hospitalizations.From 2007 to 2021, there were 370,756 breast cancer cases. Using net survival, 318,429 (85.9%) of these patients were projected to survive breast cancer by 2022, a prevalence of 2.1% of Canadian women. Using overall survival, prevalence was 1.8%. Prevalence increased with age group, from 0.01% of those aged 20 to 24 years to 12.7% of those aged ≥90 years, and from 1.0% among the working and/or child-raising (age 20-64 years) to 5.4% among elderly populations (age ≥65 years). Among these survivors, 24.9% of projected heart failure hospitalizations would be in excess of those among matched control subjects, with projected excess costs of $16.5 million CAD. Given the excess healthcare costs, potential for reduced contributions to the workforce, and reduced quality of life associated with long-term impairments and risk of excess non-breast cancer death, enhanced breast cancer survivorship care is warranted.With an overall prevalence of 2% among Canadian women, breast cancer survivors represent an increasing segment of the working-age and elderly populations.